ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.1196A>G (p.Glu399Gly) (rs117898549)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000340961 SCV000358535 uncertain significance Renal dysplasia and retinal aplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000389927 SCV000358536 uncertain significance Nephronophthisis 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000766889 SCV000618972 uncertain significance not provided 2017-07-18 criteria provided, single submitter clinical testing The c.1196A>G variant in the NPHP4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1196A>G variant is observed in 82/8578 (0.96%) alleles from individuals of East Asian background, in the ExAC dataset (Lek et al., 2016). In-silico splice models predict that c.1196A>G may create a cryptic splice acceptor site in exon 10 that could supplant the natural splice acceptor site. However, in the absence of RNA/functional studies, the actual effect of the c.1196A>G change in this individual is unknown. If c.1196A>G does not alter splicing, it will result in the E399G missense change.The E399G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Glutamic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret c.1196A>G as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000523327 SCV000701723 likely benign not specified 2016-09-28 criteria provided, single submitter clinical testing
Invitae RCV000766889 SCV001004822 benign not provided 2018-01-02 criteria provided, single submitter clinical testing

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